[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/all2en\/wiki32\/beta-amyloid-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/all2en\/wiki32\/beta-amyloid-wikipedia\/","headline":"Beta-amyloid \u2014 Wikipedia","name":"Beta-amyloid \u2014 Wikipedia","description":"The beta amyloid peptide or \u03b2-amylo\u00efde is a peptide (a small protein) belonging to the family of amyloid substances. In","datePublished":"2017-07-01","dateModified":"2017-07-01","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/all2en\/wiki32\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/all2en\/wiki32\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/44a4cee54c4c053e967fe3e7d054edd4?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/44a4cee54c4c053e967fe3e7d054edd4?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/3\/38\/Info_Simple.svg\/12px-Info_Simple.svg.png","url":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/3\/38\/Info_Simple.svg\/12px-Info_Simple.svg.png","height":"12","width":"12"},"url":"https:\/\/wiki.edu.vn\/all2en\/wiki32\/beta-amyloid-wikipedia\/","wordCount":3150,"articleBody":" The beta amyloid peptide or \u03b2-amylo\u00efde is a peptide (a small protein) belonging to the family of amyloid substances. In certain circumstances, it is harmful to the central nervous system (under the influence of different genetic and environmental factors still misunderstood [ first ] ). The beta amyloid is at the center of the amyloid hypothesis which is the theory, initially formulated by JA Hardy and Ga Higgins in 1992, according to which Alzheimer’s disease is caused by the presence of amyloid plates in the brain. This theory has led to the development of numerous research for the development of drugs. However, controversy appeared in the United States in 2021 concerning its reality and the integrity of certain scientific articles underlying it.   \u0392-amyloid peptides are proteins from 36 to 43 amino acids. They are mainly located in the brain but can also be found in the blood circulation. It comes from the precursor of the amyloid (app), transmembrane glycoprotein which has functions in synaptogenesis, neuronal migration, cellular adhesion and cell signaling. The gene coding protein precursor of the amyloid is located on the locus q21.2 chromosome 21. The pioneer protein of the amyloid can be cleared in two ways: Using the non-amyloidogenic path, which consists of a cut by alpha-secretase. This one closes in the center of the beta-amyloid and gives an essential protein for neuronal plasticity; Using the amyloidogenic path which consists of a cut by beta-spec\u00e9tase and by gamma-spec\u00e9tase. These will click respectively the n-terminal and c-terminal parts of the beta-amyloid. As the years go by, alpha-spec\u00e9tase is replaced by beta-secretase.So, as they get older, neurons have more difficulty transmitting a nervous influx. When cleaved in position 42 (A\u03b242) and not 40 (A\u03b240), beta amyloid peptide lowers the effectiveness of cholinergic transmission. There are several hypotheses explaining this action, here are two: The hypothesis of inflammation : amyloid peptides aggregate and forms of amyloid plates. The latter are phagocytized by microglia (macrophages of the central nervous system) which induces an inflammatory reaction. Insofar as this inflammatory reaction is prolonged, this induces the death of the cholinergic neurons of the brocca diagonal strip and the basal nucleus of Meynert; Cholinergic hypothesis : A\u03b242 will decrease choline’s reuptake by the DAT channel (Dopamine Transporter). This channel, as its name suggests, is necessary for choline reuptake by the presynaptic button. This leads to a drop in choline in the neuron. To counter this drop, the neuron will make membrane autophagy, that is to say breaking its membrane to release phosphatidylcholine which is a rich source of choline. It will reduce the activity of acetyltransferase choline, the enzyme necessary for the formation of acetylcholine from acetyle and choline. This reduction also leads to a decrease in synaptic transmission. She will finally modulate the reception of acetylcholine by reducing the activity of muscarinic receivers. This drop once again leads to a decrease in cholinergic transmission. In 2006, Sylvain len\u00e9 from the University of Minnesota, Twin Cities, published in Nature an article [ 2 ] which underlies the dominant but controversial amyloid hypothesis of Alzheimer’s disease, according to which A\u03b2 agglutinates. In July 2022 , this article was cited by more than 2,300 scientific publications [ 3 ] . Several diseases would be connected to the aggregation Beta-amyloid. Vaccination is also the subject of research (active immunotherapy). “The second approach is based on the injection of a close structure peptide, to stimulate the immune system and increase its effectiveness in eliminating amyloid proteins that accumulate in the brain” [ first ] . According to clinical trials, this strategy induces an immune reaction, but without apparent reduction in symptoms [ first ] . A track would be to apply treatment earlier, before the appearance of symptoms, but this raises ethical questions related to the very early diagnosis of an incurable but often quite late disease [ first ] . Immunotherapy is the most explored track: highly specific antibodies are directed against peptide (passive immunotherapy). After the failure of a trial on more than 2100 patients, the November 23, 2016 Eli Lilly (company having developed Solanezumab) publicly announced that it abandoned this medication for the treatment of patients with the start of dementia. This molecule which had aroused great hopes [ 4 ] Added to the many other anti-amyloids tested to date, all without success [ 5 ] . However, the Donanemab, directed against the amyloid beta in the form of plates, seems to give some results in the early forms [ 6 ] . In August 2021, the American Food and Drug Administration (FDA) received a citizen petition asking to stop the simfilam clinical trials based mainly on alleged anomalies in the images of preclinical articles. Following the advertising of allegations, other scientists also questioned these results, citing the small size of the sample, the alleged methodological defects of an in vitro technique, the alleged manipulations of Western Blot images and Potential conflicts of interest [ 7 ] . Reuters reported on July 27, 2022 that a criminal investigation into Cassava Sciences had been opened by the United States Ministry of Justice (DoJ) on research results related to the experimental drug against Alzheimer’s disease [ 8 ] . The Wall Street Journal said that the Securities and Exchange Commission (SEC) of the United States and the American Center for Diseases (National Institute of Health, NIH) also investigate data manipulation by Cassava [ 9 ] . In August 2021, Matthew Schrag, a doctor and neuroscientist at Vanderbilt University, was approached by a lawyer working on the Simulfan file. The elements he discovered were then divided by this lawyer in the petition at the FDA, and by Matthew Schrag at the NIH. The magazine Science Then conducted a six -month investigation including the Revue des suspicions and questions raised by Schrag on the research work of Les\u00e9 by research specialists on Alzheimer’s. Science Also asked Elisabeth Bik and Jana Christopher to analyze this work. These works have confirmed the suspicions of scientific fraud by image manipulation on twenty publications of Lesn\u00e9, of which ten on A\u03b2*56. Science rendered his public conclusions in an article of July 2022 [ 3 ] . \u2191 A B C and D Case Alzheimer , Inserm, consulted first is \u00a0sept 2016.  \u2191 (in) LESN\u00c1, S., KOH, M., Kotilinek, L. et al. , ‘ A specific amyloid-\u03b2 protein assembly in the brain impairs memory \u00bb , Nature 440, 352\u2013357 , 2006 ( read online ) .  \u2191 a et b (in) Charles pills, ‘ BLOTS ON A FIELD? A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer\u2019s articles, threatening a reigning theory of the disease \u00bb , Science , July 21, 2022 ( read online  ) .  \u2191 (in) Elie Dolgin (2016) How to defeat dementia Three things are needed to turn the tide on the costliest crisis in health care , 09 November 2016.  \u2191 (in) Alison Abbott & Elie Dolgin (2016) Failed Alzheimer\u2019s trial does not kill leading theory of disease  The drug, and others based on the \u2018amyloid hypothesis\u2019, are still being tested in other, different trials ; published in the newspaper Nature on 23 November 2016; DOI: 10.1038\/Nature.2016.21045.  \u2191 MINTUN MA, Lo AC, duggan evs C et al. Donanemab in early Alzheimer\u2019s disease , N Engl j with , 2021; 384: 1691-1704  \u2191 (in) Mandavilli, Apoorva, ‘ Scientists Question Data Behind an Experimental Alzheimer’s Drug \u00bb , The New York Times , April 18, 2022 ( read online  ) .  \u2191 (in) Marisa Taylor, Mike Spector, ‘ Exclusive: Cassava Sciences faces U.S. criminal probe tied to Alzheimer’s drug, sources say \u00bb , Reuters , July 27, 2022 ( read online  ) .  \u2191 (in) Michaels, Dave; Walker, Joseph, ‘ SEC Investigating Cassava Sciences, Developer of Experimental Alzheimer’s Drug \u00bb , The Wall Street Journal , November 17, 2021 (ISSN\u00a0 0099-9660 , read online ) .  On other Wikimedia projects: Related articles [ modifier | Modifier and code ] external links [ modifier | Modifier and code ]  "},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/all2en\/wiki32\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/all2en\/wiki32\/beta-amyloid-wikipedia\/#breadcrumbitem","name":"Beta-amyloid \u2014 Wikipedia"}}]}]